Abstract

Repeated exposure of adult rats to a variety of psychoactive compounds can result in altered behavioral responsiveness to later exposures depending on the dose, route, and frequency of administration and time of testing. The ontogeny and mechanism of this altered responsiveness are not well understood. To determine when behavioral sensitization to phencyclidine (PCP) occurs, neonatal and early developmental exposure effects of PCP were assessed on later behavioral responsiveness to a PCP challenge. Rat pups were injected daily for nine days beginning on either postnatal days (PNDs) 1 or 22 with 0.9% saline, 5.0 or 10.0 mg/kg PCP-HC1 (s.c.). Ten days following the last injection, rats were given one of the following drug challenges: 0.9% saline, 5.0 or 10.0 mg/kg PCP-HC1 (s.c.). Locomotor activity, ataxia, and several other behaviors were measured for 1 h beginning 2-3 min after the challenge injection. Two major findings emerged from these studies. First, pups treated subchronically with PCP on PNDs 1-9 did not exhibit any difference in behavioral sensitivity to a PCP challenge when tested on PND 19 compared to subchronically treated saline controls. In contrast, pups subchronically treated with PCP on PNDs 22-30 exhibited an increased sensitivity to the behavioral effects of a PCP challenge. These data suggest that PCP has age-dependent exposure effects that occur sometime after the first postnatal week and that result in an enhanced behavioral responsiveness to PCP later in life.